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DOI: 10.1055/s-2008-1078272
An Efficient Protocol for Multicomponent Stereoselective Synthesis of 3-Amino-2(1H)-pyridinones Using CeCl3˙7H2O/NaI as a Reaction Promoter
Publication History
Publication Date:
21 August 2008 (online)
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Abstract
An efficient and convenient diastereoselective synthesis of 3-amino-2(1H)-pyridinones by CeCl3˙7H2O/NaI-promoted [3+2+1] three-component coupling reactions of chalcones, 2-phenyl-1,3-oxazolon-5-one, and amines is reported. The protocol involves sequential Michael addition, condensation, ring transformation, and acid hydrolysis. Operational simplicity, ambient temperature, high yields, and diastereoselectivity are the key features of the present synthetic protocol. The reaction is an excellent illustration of Ce(III)-catalyzed C-C and C-N bond formations in a one-pot procedure
Key words:
multicomponent reaction - Lewis acid - chalcones - heterocycles - stereoselective synthesis
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References and Notes
General Procedure
for the Synthesis of 3-Benzamido-2 (1
H
)-pyridinones 5
A mixture of 1,3-oxazolon-5-one 1 (5 mmol), chalcone 2 (5 mmol),
amine 3 (5 mmol), CeCl3˙7H2O
(1 mmol), and NaI (1 mmol) in EtOH (25 mL) was stirred at r.t. for
3-5 h. After completion of the reaction, as indicated by
TLC (hexane-EtOAc, 8:2, v/v), the solvent was
evaporated under reduced pressure, the residue thus obtained extracted
with Et2O (3 × 15 mL). The
extract was evaporated to leave the crude product which was recrystallized
from EtOH to afford a distereomeric mixture (>96:<4;
in the crude products the ratio was >94:6 as indicated
by ¹H NMR spectroscopy). The product on second
recrystallization from EtOH furnished analytically pure pale yellow
crystal of a single diastereomer 4, which
was assigned the trans stereochemistry
on the basis of ¹H NMR spectra.
Characterization
Data for Representative Compounds
Compound 7 (Ar¹ = Ar² = R = Ph):
pale yellow crystals; yield 82%; mp 124-125 ˚C.
IR (KBr): νmax = 3340,
3023, 1745, 1642, 1605, 1585, 1455, 755, 712 cm.-¹. ¹H
NMR (400 MHz, DMSO-d
6 and
D2O-TMS): δ = 3.99
(d, 1 H, J = 10.0 Hz,
3-H), 4.19 (dd, 1 H, J = 10.0,
5.9 Hz, 4-H), 5.93 (d, 1 H, J = 5.9
Hz, 5-H), 7.10-7.70 (m, 20 Harom). ¹³C
NMR(100 MHz, DMSO-d
6): δ = 39.9,
59.0, 114.2, 117.6, 119.0, 120.1, 121.3, 124.0, 125.2, 126.4, 127.5,
128.5, 129.6, 130.8, 132.0, 133.1, 134.2, 135.5, 137.4, 143.4, 172.6,
174.2. MS (EI): m/z = 444 [M+].
Anal. Calcd for C30H24N2O2:
C, 81.06; H, 5.44; N, 6.30. Found: C, 80.70; H, 5.74; N, 6.10.
Compound 7 (Ar¹ = 4-MeOC6H4;
Ar² = R = Ph):
pale yellow crystals; yield 80%; mp 133-134 ˚C.
IR (KBr): 3340, 3021, 1742, 1640, 1600, 1582, 1400, 752, 710 cm.-¹. ¹H NMR
(400 MHz, DMSO-d
6 and D2O-TMS): δ = 3.79
(s, 3 H, OMe), 4.01 (d, 1 H, J = 10.0
Hz, 3-H), 4.18 (dd, 1 H, J = 10.0,
5.9 Hz, 4-H), 5.99 (d, 1 H, J = 5.9
Hz, 5-H), 7.18-7.99 (m, 19 Harom). ¹³C
NMR (100 MHz, DMSO-d
6): δ = 39.2,
56.0, 59.2, 114.0, 117.5, 119.2, 120.3, 122.4, 124.0, 125.1, 126.2,
127.3, 128.3, 129.4, 130.5, 131.6, 132.9, 134.0, 135.2, 137.5, 143.9,
172.9, 174.8. MS (EI):
m/z = 474 [M+].
Anal. Calcd for C31H26N2O3:
C, 78.46; H, 5.52; N, 5.90. Found: C, 78.81; H, 5.30; N, 5.56.
General Procedure
for the Synthesis of 3-Amino-2 (1
H
)-Pyridinone 4
Compound 5 (2.0 mmol) was refluxed in H2SO4-H2O
(15 mL, 4:3, v/v) for 30 min in an oil bath. The reaction
mixture was cooled, filtered, and the desired product 4 was precipitated by adding concentrated
NH4OH (d = 0.88) under ice
cooling and recrystallized from EtOH to afford an analytically pure
sample of 4 (Table
[¹]
).
Characterization
Data for Representative Compounds
Compound 4 (Table
[²]
,
entry 1): pale yellow crystals; yield 90%; mp 135-134 ˚C.
IR (KBr): 3342, 3011, 1699, 1608, 1540, 1430, 749, 703 cm-¹. ¹H
NMR (400 MHz, DMSO-d
6 and
D2O-TMS): δ = 3.96
(d, 1 H, J = 9.9
Hz, 3-H), 4.15 (dd, 1 H, J = 9.9,
5.9 Hz, 4-H), 5.90 (d, 1 H, J = 5.9
Hz, 5-H), 7.19-7.90 (m, 15 Harom). ¹³C
NMR(100 MHz, DMSO-d
6
): δ = 39.7,
58.5, 114.0, 120.0, 122.1, 125.0, 126.2, 127.4, 128.7, 129.8, 130.8,
131.9, 133.0, 134.7, 141.0, 143.0, 172.6. MS (EI): m/z = 340 [M+].
Anal. Calcd for C23H20N2O: C, 81.15;
H, 5.92; N, 8.23. Found: C, 80.83; H, 5.62; N, 8.43.
Compound 4 (Table
[²]
,
entry 7): pale yellow crystals; yield 87%; mp 140-141 ˚C.
IR (KBr): νmax = 3340,
3021, 1742, 1640, 1600, 1582, 1400, 752, 710 cm-¹. ¹H
NMR (400 MHz, DMSO-d
6 and
D2O-TMS): δ = 3.78
(s, 3 H, OMe), 3.98 (d, 1 H, J = 9.9
Hz, 3-H), 4.13 (dd, 1 H, J = 9.9,
5.9 Hz, 4-H), 5.92 (d, 1 H, J = 5.9
Hz, 5-H), 7.19-7.86 (m, 14 Harom). ¹³C
NMR (100 MHz, DMSO-d
6
): δ = 39.2,
55.6, 58.3, 114.1, 120.2, 122.0, 125.1, 126.3, 127.5, 128.5, 129.8,
130.9, 132.0, 133.6, 134.8, 141.2, 144.0, 172.4. MS (EI): m/z = 370 [M+].
Anal. Calcd for C24H22N2O2:
C, 77.81; H, 5.99; N, 7.56. Found: C, 78.12; H, 6.29; N, 7.26.